RRC ID 39761
Author Yoshikawa K, Ogawa T, Baer R, Hemmi H, Honda K, Yamauchi A, Inamoto T, Ko K, Yazumi S, Motoda H, Kodama H, Noguchi S, Gazdar AF, Yamaoka Y, Takahashi R.
Title Abnormal expression of BRCA1 and BRCA1-interactive DNA-repair proteins in breast carcinomas.
Journal Int J Cancer
Abstract Breast cancer is one of the most common malignancies among women. The molecular mechanisms involved in breast carcinogenesis, however, remain to be elucidated. Although somatic mutation of BRCA1 is rare, BRCA1 protein expression is reduced in about 30% of sporadic breast carcinomas (Yoshikawa et al., Clin. Cancer Res., 5:1249-1261, 1999), indicating its possible involvement even in sporadic breast carcinogenesis. Among the BRCA1-interactive proteins are hRAD51 (a human homologue of Escherichia coli rec A protein), BARD1 (BRCA1-associated RING domain 1) and p53, all of which are involved in DNA repair. We have analyzed the expression patterns of the hRAD51, BARD1 and p53 proteins in five breast cancer cell lines, including a BRCA1-deficient cell line, and in 179 breast cancer tissue samples from Japanese women, including 113 sporadic, 47 hereditary (i.e., BRCA1 status unknown), and 19 BRCA1-associated cases. Of the 179 breast carcinomas, fifty-four (30%) exhibited reduced hRAD51 expression, and sixty-two (35%) exhibited p53 overexpression. On the other hand, reduced expression level of BARD1, and of hMSH2 and hMLH1, which are components of DNA mismatch-repair pathway and are involved in colorectal carcinogenesis, was observed respectively in only 10 (6%), 8 (5%) and 3 (2%) cases. The overall frequency of sporadic breast carcinomas with abnormal expression of either BRCA1 or the BRCA1-interactive proteins was 67% (76/113). These results indicate that there may be an important role for the BRCA1-associated DNA-repair pathway, not only in BRCA1-associated breast carcinomas, but also in sporadic breast carcinomas.
Volume 88(1)
Pages 28-36
Published 2000-10-1
PII 10.1002/1097-0215(20001001)88:1<28::AID-IJC5>3.0.CO;2-4
PMID 10962436
MeSH Adaptor Proteins, Signal Transducing Animals BRCA1 Protein / biosynthesis* BRCA1 Protein / genetics Breast / cytology Breast / metabolism Breast Neoplasms / genetics Breast Neoplasms / metabolism* Breast Neoplasms / pathology Carrier Proteins / biosynthesis Carrier Proteins / genetics DNA Repair / physiology* DNA-Binding Proteins / biosynthesis DNA-Binding Proteins / genetics Epithelial Cells / metabolism Epithelial Cells / pathology Female Gene Expression Genes, BRCA1 Germ-Line Mutation Humans Immunohistochemistry Middle Aged MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins / biosynthesis* Neoplasm Proteins / genetics Neoplasm Transplantation Nuclear Proteins Proliferating Cell Nuclear Antigen / biosynthesis Proto-Oncogene Proteins / biosynthesis Proto-Oncogene Proteins / genetics Rad51 Recombinase Rats Rats, Nude Receptor, ErbB-2 / biosynthesis Receptor, ErbB-2 / genetics Receptors, Estrogen / biosynthesis Tumor Cells, Cultured Tumor Suppressor Protein p53 / biosynthesis Tumor Suppressor Protein p53 / genetics Tumor Suppressor Proteins* Ubiquitin-Protein Ligases*
IF 5.145
Times Cited 79
Human and Animal Cells HBL-100(RCB0460)